Role of α1-adrenergic antagonist activity and 5-HT1A antagonism in the occurrence of ischaemic stroke and TIA within one year after a first prescription of antipsychotics in France: a cohort study in the EGB between 2009 and 2019

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Pharmacodynamic study

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N05A) ANTIPSYCHOTICS

  ANTIPSYCHOTICS

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  33120

Study design details

• Main study objective:
  Evaluate whether prescribing antipsychotic drugs with high α1-blocker affinity and 5-HT1A antagonist activity is associated with an increased risk of hospitalisation for ischaemic stroke or transient ischaemic attack (TIA) within one year of initiation, compared with prescribing antipsychotic drugs with low α1-adrenergic affinity and absence of 5-HT1A antagonism (reference group).
• Outcomes:
  Difference in survival without hospitalisation for ischaemic stroke (ICD code I63) or transient ischaemic attack (G45) during the follow-up period in the cohort, between the two exposure groups. Occurrence of a hospitalization with a principal diagnosis of ischemic stroke (ICD code I63) during the follow-up period in the cohort. Occurrence of a hospitalization with a principal diagnosis of TIA (G45) during the follow-up period in the cohort. Death during the follow-up period in the cohort.
• Data analysis plan:
  Main analysis : Statistical analyses will be performed without blinding procedures. The main analysis will be performed as treated. The crude incidence rate of occurrence of the primary endpoint will be estimated in each exposure group. The 12-month risk of hospitalisation for ischemic cerebrovascular events will be estimated by Kaplan-Meier analysis for both exposure groups. We will use a Cox proportional hazards regression model to estimate Hazard Ratios (HRs) and their 95% confidence intervals for the risk of occurrence of the primary endpoint of the "strong α1-blocker-5-HT1A antagonist" antipsychotic group, compared with the "weak α1-blocker-non-5-HT1A antagonist" antipsychotic group. Sensitivity and additional analyses : cf. protocol.